A5049454660- Advanced biosensing and bioanalysis techniques
- Cystic Fibrosis Research Advances
- Mitochondrial Function and Pathology
- Energy Harvesting in Wireless Networks
- Glioma Diagnosis and Treatment
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Neonatal Respiratory Health Research
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Neurogenetic and Muscular Disorders Research
Stony Brook University
2021-2023
Cold Spring Harbor Laboratory
2021-2023
University of California, Los Angeles
2022
In Huntington's disease (HD), the uninterrupted CAG repeat length, but not polyglutamine predicts onset. However, underlying pathobiology remains unclear. Here, we developed bacterial artificial chromosome (BAC) transgenic mice expressing human mutant huntingtin (mHTT) with uninterrupted, and somatically unstable, repeats that exhibit progressive disease-related phenotypes. Unlike prior mHTT models stable, CAA-interrupted, polyglutamine-encoding repeats, BAC-CAG show robust...
Significance Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator ( CFTR ) gene, which can lead to respiratory failure. To date, there no treatment for CF CFTR- W1282X mutation located on exon 23. Nonsense-mediated messenger RNA (mRNA) decay (NMD) degrades mRNA, leading low levels of functional protein. We developed a cocktail two antisense oligonucleotides (ASOs) that promotes skipping 23 mRNA. The resulting mRNA NMD resistant and preserves reading...
Diffuse midline gliomas (DMGs) are pediatric high-grade brain tumors in the thalamus, midbrain, or pons; latter subgroup termed diffuse intrinsic pontine (DIPG). The stem location of these limits clinical management DIPG, resulting poor outcomes for patients. A heterozygous, somatic point mutation one two genes coding noncanonical histone H3.3 is present most DIPG tumors. This dominant H3-3A gene results replacement lysine 27 with methionine (K27M) and causes a global reduction...
Abstract Low CFTR mRNA expression due to nonsense-mediated decay (NMD) is a major hurdle in developing therapy for cystic fibrosis (CF) caused by the W1282X mutation gene. CFTR-W1282X truncated protein retains partial function, so increasing its levels inhibiting NMD of will likely be beneficial. Because regulates normal many genes, gene-specific stabilization CFTR- more desirable than general inhibition. Synthetic antisense oligonucleotides (ASOs) designed prevent binding exon junction...
Abstract Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene cause (CF), and CFTR-W1282X nonsense mutation causes a severe form of CF. Although Trikafta other CFTR-modulation therapies benefit most CF patients, targeted therapy for patients with W1282X is lacking. The protein has residual activity, but expressed at very low level due to nonsense-mediated mRNA decay (NMD). NMD-suppression read-through are actively being researched mutants. NMD suppression could...